Injury-induced NF-kappaB activation in the hippocampus: implications for neuronal survival.

Nuclear factor (NF)-kappaB p50 protein is involved in promoting survival in hippocampal neurons after trimethyltin (TMT)-injury. In the current study, hippocampal NF-kappaB activity was examined and quantitated from transgenic kappaB-lacZ reporter mice after chemical-induced injury. NF-kappaB activity was localized primarily to hippocampal neurons and significantly elevated over that in saline-treated mice between 4 and 21 days after TMT injection. Seven days after TMT injection, a timepoint of elevated NF-kappaB activity, gene expression in the hippocampus was studied by microarray analysis through comparison of expression profiles between treated nontransgenic and p50-null mice with their saline-injected controls. Seventeen genes increased in nontransgenic TMT-treated mice relative to saline-treated as well as showing no increase in p50-null mice, indicating a role for p50 in their regulation. One of these genes, the Na+, K+-ATPase-gamma subunit, was detected in brain for the first time. Several of the genes modulated by NF-kappaB are potentially related to neuroplasticity, providing additional evidence that this transcription factor is a neuroprotective signal in the hippocampus.